Analysis of the complexation of gemfibrozil with γ- and hydroxypropyl-γ-cyclodextrins

The interactions of gemfibrozil with γ- and HP-γ-cyclodextrin (CD) have been studied in aqueous solution by fluorescence and NMR spectroscopy and by solubility measurements and in the solid state by X-ray diffraction, thermal analysis and FTIR spectroscopy. The influence of the technique employed in the analysis of complexation is discussed. The fluorescence of gemfibrozil increased in the presence of γ- and hydroxypropyl-γ-cyclodextrin (HP-γ-CD), especially with the later, because the inclusion of the aromatic ring in the cavity, evidenced by 1H NMR, has a protective effect on the excited state of the drug. The fluorescence enhancement allowed the determination of the binding constants at pH 2.8. Complexation was a both entropy and enthalpy driven process. The solubility diagrams obtained with γ-CD and HP-γ-CD were Bs and AL type, respectively. The apparent stability constants calculated from the solubility data at 25 °C were compared with those obtained from the fluorescence assays. It was found that drug solubilization with γ-CD involves other contributions together with the inclusion phenomena. Solid complexes of gemfibrozil with γ-CD (and not with HP-γ-CD) have been obtained by kneading, coevaporation and coprecipitation methods. The solid complexes crystallised in the channel structure, in a process involving the carboxyl and aryl-ether groups.